DOI: 10.1002/prot.1134. Protein molecular dynamics with the generalized born/ACE solvent model

Protein molecular dynamics with the generalized born/ACE solvent model

10.1002/prot.1134

Crossref journal-article

Wiley

Proteins: Structure, Function, and Bioinformatics (311)

Abstract

AbstractImplicit solvent models are increasingly important for the study of proteins in aqueous solution. Here, the generalized Born (GB) solvent polarization model as implemented in the analytical ACE potential [Schaefer and Karplus (1996) J Phys Chem 100:1578] is used to perform molecular dynamics simulations of two small, homologous proteins: the immunoglobulin‐binding domain of streptococcal protein G and the Ras binding domain of Raf. Several model parameterizations are compared through more than 60 ns of simulation. Results are compared with two simpler solvent models—an accessible surface area model and a distant‐dependent dielectric model, with finite‐difference Poisson calculations, with existing explicit solvent simulations, and with experimental data. The simpler models yield stable but distorted structures. The best GB/ACE implementation uses a set of atomic Voronoi volumes reported recently, obtained by averaging over a large database of crystallographic protein structures. A 20% reduction is applied to the volumes, compensating in an average sense for an excessive de‐screening of individual charges inherent in the ACE self‐energy and for an undersolvation of dipolar groups inherent in the GB screening function. This GB/ACE parameterization yields stable trajectories on the 0.5–1‐ns time scale that deviate moderately (∼1.5–2.5 Å) from the X‐ray structure, reproduce approximately the surface distribution of charged, polar, and hydrophobic groups, and reproduce accurately backbone flexibility as measured by amide NMR‐order parameters. Over longer time scales (1.5–3 ns), some of the protein G runs escape from the native energy basin and deviate strongly (3 Å) from the native structure. The conformations sampled during the transition out of the native energy basin are overstabilized by the GB/ACE solvation model, as compared with a numerical treatment of the full dielectric continuum model. Proteins 2001;45:144–158. © 2001 Wiley‐Liss, Inc.

Bibliography

Calimet, N., Schaefer, M., & Simonson, T. (2001). Protein molecular dynamics with the generalized born/ACE solvent model. Proteins: Structure, Function, and Bioinformatics, 45(2), 144â158. Portico.

Authors 3

Nicolas Calimet (first)
Michael Schaefer (additional)
Thomas Simonson (additional)

References 73 Referenced 102

10.1002/9780470141205.ch1
10.1201/9780203903827
10.1016/S0301-4622(98)00226-9
10.1021/cr990052a
10.1016/S0959-440X(00)00197-4
10.1002/pro.5560010204
10.1006/jmbi.1996.0139
10.1002/(SICI)1097-0134(19990501)35:2<133::AID-PROT1>3.0.CO;2-N
10.1063/1.1750302
10.1146/annurev.bb.19.060190.001505 / Annu Rev Biophys Biophys Chem / Electrostatic interactions in macromolecules: Theory and applications by Sharp K (1991)
10.1016/S0065-3233(08)60650-6
10.1002/jcc.540120407
10.1021/j100058a043
10.1021/j100068a033
10.1021/jp970736r
{'key': 'e_1_2_6_17_2', 'volume-title': 'Electrodynamics of continuous media', 'author': 'Landau L', 'year': '1980'} / Electrodynamics of continuous media by Landau L (1980)
{'key': 'e_1_2_6_18_2', 'volume-title': 'Theory of dielectrics', 'author': 'Fröhlich H', 'year': '1949'} / Theory of dielectrics by Fröhlich H (1949)
10.1021/ja00135a018
10.1021/jp963412w
10.1021/jp991354j
10.1021/ja984414s
10.1021/jp984327m
10.1002/jcc.540160904
10.1002/(SICI)1096-987X(19990715)20:9<956::AID-JCC7>3.0.CO;2-R
10.1021/jp994349o
10.1063/1.1348028
10.1021/j100116a025
{'key': 'e_1_2_6_29_2', 'first-page': '1', 'article-title': 'Continuum solvation model: Computation of electrostatic forces from numerical solutions to the Poisson–Boltzmann equation', 'volume': '109', 'author': 'Im W', 'year': '1998', 'journal-title': 'Comp Phys Commun'} / Comp Phys Commun / Continuum solvation model: Computation of electrostatic forces from numerical solutions to the Poisson–Boltzmann equation by Im W (1998)
10.1002/(SICI)1096-987X(200003)21:4<295::AID-JCC5>3.0.CO;2-8
10.1021/ja00172a038
10.1146/annurev.physchem.51.1.129
10.1021/jp9714227
10.1016/S0022-2836(99)80019-9
10.1016/0009-2614(95)01082-K
10.1021/jp9521621
10.1021/jp961992r
10.1021/jp982533o
10.1021/jp971035x
10.1021/jp980506s
10.1002/(SICI)1096-987X(199902)20:3<322::AID-JCC4>3.0.CO;2-Q
10.1021/jp984440c
10.1006/jmbi.1998.2172
10.1021/ja981844
10.1021/jp994072s
10.1002/(SICI)1097-0134(19991001)37:1<88::AID-PROT9>3.0.CO;2-O
10.1016/S0006-3495(99)77471-0
10.1021/ja9939385
10.1021/jp0027602
10.1007/s002140050429
10.1002/jcc.1137
10.1002/(SICI)1097-0134(199710)29:2<193::AID-PROT7>3.0.CO;2-E
10.1007/BF01881023
SchaeferM.Monte Carlo–Dynamik und Elektrostatik von Proteinen. PhD thesis Heidelberg University;1989.
10.1038/248338a0
10.1021/ja00372a001
10.1002/jcc.540040211
10.1021/j100374a057
10.1021/bi00507a030
10.1002/bip.360320608
10.1002/prot.340040208
ReiherWE.Theoretical studies of hydrogen bonding. PhD thesis Harvard University;1985.
10.1016/0021-9991(77)90098-5
10.1016/0010-4655(95)00043-F
10.1021/cr00101a005
10.1002/jcc.540090407
10.1016/0022-2836(73)90011-9
10.1002/jcc.540120718
10.1002/jcc.540150702
10.1016/0022-2836(92)90136-8
{'key': 'e_1_2_6_71_2', 'volume-title': 'Static and dynamic electricity', 'author': 'Smythe W', 'year': '1968'} / Static and dynamic electricity by Smythe W (1968)
10.1073/pnas.96.20.11145
10.1107/S0021889891004399
10.1002/pro.5560030103

Dates

Type	When
Created	23 years ago (Aug. 25, 2002, 5:24 p.m.)
Deposited	1 year, 10 months ago (Oct. 16, 2023, 12:26 a.m.)
Indexed	1 month, 1 week ago (July 25, 2025, 6:19 a.m.)
Issued	24 years ago (Aug. 22, 2001)
Published	24 years ago (Aug. 22, 2001)
Published Online	24 years ago (Aug. 22, 2001)
Published Print	23 years, 10 months ago (Nov. 1, 2001)

Funders 0

None

BibTeX

@article{Calimet_2001, title={Protein molecular dynamics with the generalized born/ACE solvent model}, volume={45}, ISSN={1097-0134}, url={http://dx.doi.org/10.1002/prot.1134}, DOI={10.1002/prot.1134}, number={2}, journal={Proteins: Structure, Function, and Bioinformatics}, publisher={Wiley}, author={Calimet, Nicolas and Schaefer, Michael and Simonson, Thomas}, year={2001}, month=aug, pages={144–158} }

JSON

{
  "indexed": {
    "date-parts": [
      [
        2025,
        7,
        25
      ]
    ],
    "date-time": "2025-07-25T10:19:10Z",
    "timestamp": 1753438750994
  },
  "reference-count": 73,
  "publisher": "Wiley",
  "issue": "2",
  "license": [
    {
      "start": {
        "date-parts": [
          [
            2001,
            8,
            22
          ]
        ],
        "date-time": "2001-08-22T00:00:00Z",
        "timestamp": 998438400000
      },
      "content-version": "vor",
      "delay-in-days": 0,
      "URL": "http://onlinelibrary.wiley.com/termsAndConditions#vor"
    }
  ],
  "content-domain": {
    "domain": [],
    "crossmark-restriction": false
  },
  "published-print": {
    "date-parts": [
      [
        2001,
        11
      ]
    ]
  },
  "abstract": "<jats:title>Abstract</jats:title><jats:p>Implicit solvent models are increasingly important for the study of proteins in aqueous solution. Here, the generalized Born (GB) solvent polarization model as implemented in the analytical ACE potential [Schaefer and Karplus (1996) J Phys Chem 100:1578] is used to perform molecular dynamics simulations of two small, homologous proteins: the immunoglobulin\u2010binding domain of streptococcal protein G and the Ras binding domain of Raf. Several model parameterizations are compared through more than 60 ns of simulation. Results are compared with two simpler solvent models\u2014an accessible surface area model and a distant\u2010dependent dielectric model, with finite\u2010difference Poisson calculations, with existing explicit solvent simulations, and with experimental data. The simpler models yield stable but distorted structures. The best GB/ACE implementation uses a set of atomic Voronoi volumes reported recently, obtained by averaging over a large database of crystallographic protein structures. A 20% reduction is applied to the volumes, compensating in an average sense for an excessive de\u2010screening of individual charges inherent in the ACE self\u2010energy and for an undersolvation of dipolar groups inherent in the GB screening function. This GB/ACE parameterization yields stable trajectories on the 0.5\u20131\u2010ns time scale that deviate moderately (\u223c1.5\u20132.5 \u00c5) from the X\u2010ray structure, reproduce approximately the surface distribution of charged, polar, and hydrophobic groups, and reproduce accurately backbone flexibility as measured by amide NMR\u2010order parameters. Over longer time scales (1.5\u20133 ns), some of the protein G runs escape from the native energy basin and deviate strongly (3 \u00c5) from the native structure. The conformations sampled during the transition out of the native energy basin are overstabilized by the GB/ACE solvation model, as compared with a numerical treatment of the full dielectric continuum model. Proteins 2001;45:144\u2013158. \u00a9 2001 Wiley\u2010Liss, Inc.</jats:p>",
  "DOI": "10.1002/prot.1134",
  "type": "journal-article",
  "created": {
    "date-parts": [
      [
        2002,
        8,
        25
      ]
    ],
    "date-time": "2002-08-25T21:24:42Z",
    "timestamp": 1030310682000
  },
  "page": "144-158",
  "source": "Crossref",
  "is-referenced-by-count": 102,
  "title": "Protein molecular dynamics with the generalized born/ACE solvent model",
  "prefix": "10.1002",
  "volume": "45",
  "author": [
    {
      "given": "Nicolas",
      "family": "Calimet",
      "sequence": "first",
      "affiliation": []
    },
    {
      "given": "Michael",
      "family": "Schaefer",
      "sequence": "additional",
      "affiliation": []
    },
    {
      "given": "Thomas",
      "family": "Simonson",
      "sequence": "additional",
      "affiliation": []
    }
  ],
  "member": "311",
  "published-online": {
    "date-parts": [
      [
        2001,
        8,
        22
      ]
    ]
  },
  "reference": [
    {
      "key": "e_1_2_6_2_2",
      "doi-asserted-by": "publisher",
      "DOI": "10.1002/9780470141205.ch1"
    },
    {
      "key": "e_1_2_6_3_2",
      "doi-asserted-by": "publisher",
      "DOI": "10.1201/9780203903827"
    },
    {
      "key": "e_1_2_6_4_2",
      "doi-asserted-by": "publisher",
      "DOI": "10.1016/S0301-4622(98)00226-9"
    },
    {
      "key": "e_1_2_6_5_2",
      "doi-asserted-by": "publisher",
      "DOI": "10.1021/cr990052a"
    },
    {
      "key": "e_1_2_6_6_2",
      "doi-asserted-by": "publisher",
      "DOI": "10.1016/S0959-440X(00)00197-4"
    },
    {
      "key": "e_1_2_6_7_2",
      "doi-asserted-by": "publisher",
      "DOI": "10.1002/pro.5560010204"
    },
    {
      "key": "e_1_2_6_8_2",
      "doi-asserted-by": "publisher",
      "DOI": "10.1006/jmbi.1996.0139"
    },
    {
      "key": "e_1_2_6_9_2",
      "doi-asserted-by": "publisher",
      "DOI": "10.1002/(SICI)1097-0134(19990501)35:2<133::AID-PROT1>3.0.CO;2-N"
    },
    {
      "key": "e_1_2_6_10_2",
      "doi-asserted-by": "publisher",
      "DOI": "10.1063/1.1750302"
    },
    {
      "key": "e_1_2_6_11_2",
      "doi-asserted-by": "crossref",
      "first-page": "301",
      "DOI": "10.1146/annurev.bb.19.060190.001505",
      "article-title": "Electrostatic interactions in macromolecules: Theory and applications",
      "volume": "19",
      "author": "Sharp K",
      "year": "1991",
      "journal-title": "Annu Rev Biophys Biophys Chem"
    },
    {
      "key": "e_1_2_6_12_2",
      "doi-asserted-by": "publisher",
      "DOI": "10.1016/S0065-3233(08)60650-6"
    },
    {
      "key": "e_1_2_6_13_2",
      "doi-asserted-by": "publisher",
      "DOI": "10.1002/jcc.540120407"
    },
    {
      "key": "e_1_2_6_14_2",
      "doi-asserted-by": "publisher",
      "DOI": "10.1021/j100058a043"
    },
    {
      "key": "e_1_2_6_15_2",
      "doi-asserted-by": "publisher",
      "DOI": "10.1021/j100068a033"
    },
    {
      "key": "e_1_2_6_16_2",
      "doi-asserted-by": "publisher",
      "DOI": "10.1021/jp970736r"
    },
    {
      "key": "e_1_2_6_17_2",
      "volume-title": "Electrodynamics of continuous media",
      "author": "Landau L",
      "year": "1980"
    },
    {
      "key": "e_1_2_6_18_2",
      "volume-title": "Theory of dielectrics",
      "author": "Fr\u00f6hlich H",
      "year": "1949"
    },
    {
      "key": "e_1_2_6_19_2",
      "doi-asserted-by": "publisher",
      "DOI": "10.1021/ja00135a018"
    },
    {
      "key": "e_1_2_6_20_2",
      "doi-asserted-by": "publisher",
      "DOI": "10.1021/jp963412w"
    },
    {
      "key": "e_1_2_6_21_2",
      "doi-asserted-by": "publisher",
      "DOI": "10.1021/jp991354j"
    },
    {
      "key": "e_1_2_6_22_2",
      "doi-asserted-by": "publisher",
      "DOI": "10.1021/ja984414s"
    },
    {
      "key": "e_1_2_6_23_2",
      "doi-asserted-by": "publisher",
      "DOI": "10.1021/jp984327m"
    },
    {
      "key": "e_1_2_6_24_2",
      "doi-asserted-by": "publisher",
      "DOI": "10.1002/jcc.540160904"
    },
    {
      "key": "e_1_2_6_25_2",
      "doi-asserted-by": "publisher",
      "DOI": "10.1002/(SICI)1096-987X(19990715)20:9<956::AID-JCC7>3.0.CO;2-R"
    },
    {
      "key": "e_1_2_6_26_2",
      "doi-asserted-by": "publisher",
      "DOI": "10.1021/jp994349o"
    },
    {
      "key": "e_1_2_6_27_2",
      "doi-asserted-by": "publisher",
      "DOI": "10.1063/1.1348028"
    },
    {
      "key": "e_1_2_6_28_2",
      "doi-asserted-by": "publisher",
      "DOI": "10.1021/j100116a025"
    },
    {
      "key": "e_1_2_6_29_2",
      "first-page": "1",
      "article-title": "Continuum solvation model: Computation of electrostatic forces from numerical solutions to the Poisson\u2013Boltzmann equation",
      "volume": "109",
      "author": "Im W",
      "year": "1998",
      "journal-title": "Comp Phys Commun"
    },
    {
      "key": "e_1_2_6_30_2",
      "doi-asserted-by": "publisher",
      "DOI": "10.1002/(SICI)1096-987X(200003)21:4<295::AID-JCC5>3.0.CO;2-8"
    },
    {
      "key": "e_1_2_6_31_2",
      "doi-asserted-by": "publisher",
      "DOI": "10.1021/ja00172a038"
    },
    {
      "key": "e_1_2_6_32_2",
      "doi-asserted-by": "publisher",
      "DOI": "10.1146/annurev.physchem.51.1.129"
    },
    {
      "key": "e_1_2_6_33_2",
      "doi-asserted-by": "publisher",
      "DOI": "10.1021/jp9714227"
    },
    {
      "key": "e_1_2_6_34_2",
      "doi-asserted-by": "publisher",
      "DOI": "10.1016/S0022-2836(99)80019-9"
    },
    {
      "key": "e_1_2_6_35_2",
      "doi-asserted-by": "publisher",
      "DOI": "10.1016/0009-2614(95)01082-K"
    },
    {
      "key": "e_1_2_6_36_2",
      "doi-asserted-by": "publisher",
      "DOI": "10.1021/jp9521621"
    },
    {
      "key": "e_1_2_6_37_2",
      "doi-asserted-by": "publisher",
      "DOI": "10.1021/jp961992r"
    },
    {
      "key": "e_1_2_6_38_2",
      "doi-asserted-by": "publisher",
      "DOI": "10.1021/jp982533o"
    },
    {
      "key": "e_1_2_6_39_2",
      "doi-asserted-by": "publisher",
      "DOI": "10.1021/jp971035x"
    },
    {
      "key": "e_1_2_6_40_2",
      "doi-asserted-by": "publisher",
      "DOI": "10.1021/jp980506s"
    },
    {
      "key": "e_1_2_6_41_2",
      "doi-asserted-by": "publisher",
      "DOI": "10.1002/(SICI)1096-987X(199902)20:3<322::AID-JCC4>3.0.CO;2-Q"
    },
    {
      "key": "e_1_2_6_42_2",
      "doi-asserted-by": "publisher",
      "DOI": "10.1021/jp984440c"
    },
    {
      "key": "e_1_2_6_43_2",
      "doi-asserted-by": "publisher",
      "DOI": "10.1006/jmbi.1998.2172"
    },
    {
      "key": "e_1_2_6_44_2",
      "doi-asserted-by": "publisher",
      "DOI": "10.1021/ja981844"
    },
    {
      "key": "e_1_2_6_45_2",
      "doi-asserted-by": "publisher",
      "DOI": "10.1021/jp994072s"
    },
    {
      "key": "e_1_2_6_46_2",
      "doi-asserted-by": "publisher",
      "DOI": "10.1002/(SICI)1097-0134(19991001)37:1<88::AID-PROT9>3.0.CO;2-O"
    },
    {
      "key": "e_1_2_6_47_2",
      "doi-asserted-by": "publisher",
      "DOI": "10.1016/S0006-3495(99)77471-0"
    },
    {
      "key": "e_1_2_6_48_2",
      "doi-asserted-by": "publisher",
      "DOI": "10.1021/ja9939385"
    },
    {
      "key": "e_1_2_6_49_2",
      "doi-asserted-by": "publisher",
      "DOI": "10.1021/jp0027602"
    },
    {
      "key": "e_1_2_6_50_2",
      "doi-asserted-by": "publisher",
      "DOI": "10.1007/s002140050429"
    },
    {
      "key": "e_1_2_6_51_2",
      "doi-asserted-by": "publisher",
      "DOI": "10.1002/jcc.1137"
    },
    {
      "key": "e_1_2_6_52_2",
      "doi-asserted-by": "publisher",
      "DOI": "10.1002/(SICI)1097-0134(199710)29:2<193::AID-PROT7>3.0.CO;2-E"
    },
    {
      "key": "e_1_2_6_53_2",
      "doi-asserted-by": "publisher",
      "DOI": "10.1007/BF01881023"
    },
    {
      "key": "e_1_2_6_54_2",
      "unstructured": "SchaeferM.Monte Carlo\u2013Dynamik und Elektrostatik von Proteinen. PhD thesis Heidelberg University;1989."
    },
    {
      "key": "e_1_2_6_55_2",
      "doi-asserted-by": "publisher",
      "DOI": "10.1038/248338a0"
    },
    {
      "key": "e_1_2_6_56_2",
      "doi-asserted-by": "publisher",
      "DOI": "10.1021/ja00372a001"
    },
    {
      "key": "e_1_2_6_57_2",
      "doi-asserted-by": "publisher",
      "DOI": "10.1002/jcc.540040211"
    },
    {
      "key": "e_1_2_6_58_2",
      "doi-asserted-by": "publisher",
      "DOI": "10.1021/j100374a057"
    },
    {
      "key": "e_1_2_6_59_2",
      "doi-asserted-by": "publisher",
      "DOI": "10.1021/bi00507a030"
    },
    {
      "key": "e_1_2_6_60_2",
      "doi-asserted-by": "publisher",
      "DOI": "10.1002/bip.360320608"
    },
    {
      "key": "e_1_2_6_61_2",
      "doi-asserted-by": "publisher",
      "DOI": "10.1002/prot.340040208"
    },
    {
      "key": "e_1_2_6_62_2",
      "unstructured": "ReiherWE.Theoretical studies of hydrogen bonding. PhD thesis Harvard University;1985."
    },
    {
      "key": "e_1_2_6_63_2",
      "doi-asserted-by": "publisher",
      "DOI": "10.1016/0021-9991(77)90098-5"
    },
    {
      "key": "e_1_2_6_64_2",
      "doi-asserted-by": "publisher",
      "DOI": "10.1016/0010-4655(95)00043-F"
    },
    {
      "key": "e_1_2_6_65_2",
      "doi-asserted-by": "publisher",
      "DOI": "10.1021/cr00101a005"
    },
    {
      "key": "e_1_2_6_66_2",
      "doi-asserted-by": "publisher",
      "DOI": "10.1002/jcc.540090407"
    },
    {
      "key": "e_1_2_6_67_2",
      "doi-asserted-by": "publisher",
      "DOI": "10.1016/0022-2836(73)90011-9"
    },
    {
      "key": "e_1_2_6_68_2",
      "doi-asserted-by": "publisher",
      "DOI": "10.1002/jcc.540120718"
    },
    {
      "key": "e_1_2_6_69_2",
      "doi-asserted-by": "publisher",
      "DOI": "10.1002/jcc.540150702"
    },
    {
      "key": "e_1_2_6_70_2",
      "doi-asserted-by": "publisher",
      "DOI": "10.1016/0022-2836(92)90136-8"
    },
    {
      "key": "e_1_2_6_71_2",
      "volume-title": "Static and dynamic electricity",
      "author": "Smythe W",
      "year": "1968"
    },
    {
      "key": "e_1_2_6_72_2",
      "doi-asserted-by": "publisher",
      "DOI": "10.1073/pnas.96.20.11145"
    },
    {
      "key": "e_1_2_6_73_2",
      "doi-asserted-by": "publisher",
      "DOI": "10.1107/S0021889891004399"
    },
    {
      "key": "e_1_2_6_74_2",
      "doi-asserted-by": "publisher",
      "DOI": "10.1002/pro.5560030103"
    }
  ],
  "container-title": "Proteins: Structure, Function, and Bioinformatics",
  "original-title": [],
  "language": "en",
  "link": [
    {
      "URL": "https://api.wiley.com/onlinelibrary/tdm/v1/articles/10.1002%2Fprot.1134",
      "content-type": "unspecified",
      "content-version": "vor",
      "intended-application": "text-mining"
    },
    {
      "URL": "https://onlinelibrary.wiley.com/doi/pdf/10.1002/prot.1134",
      "content-type": "unspecified",
      "content-version": "vor",
      "intended-application": "similarity-checking"
    }
  ],
  "deposited": {
    "date-parts": [
      [
        2023,
        10,
        16
      ]
    ],
    "date-time": "2023-10-16T04:26:44Z",
    "timestamp": 1697430404000
  },
  "score": 1,
  "resource": {
    "primary": {
      "URL": "https://onlinelibrary.wiley.com/doi/10.1002/prot.1134"
    }
  },
  "subtitle": [],
  "short-title": [],
  "issued": {
    "date-parts": [
      [
        2001,
        8,
        22
      ]
    ]
  },
  "references-count": 73,
  "journal-issue": {
    "issue": "2",
    "published-print": {
      "date-parts": [
        [
          2001,
          11
        ]
      ]
    }
  },
  "alternative-id": [
    "10.1002/prot.1134"
  ],
  "URL": "http://dx.doi.org/10.1002/prot.1134",
  "relation": {},
  "ISSN": [
    "0887-3585",
    "1097-0134"
  ],
  "subject": [],
  "container-title-short": "Proteins",
  "published": {
    "date-parts": [
      [
        2001,
        8,
        22
      ]
    ]
  }
}